Optical Isomers in Pharmaceutical Products

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Optical Isomers in Pharmaceutical Products

• Johann R. Richter, Ph.D., Esq.
• SPE 1616
• 571-272-0646
• johann.richter_at_uspto.gov

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Definition of Isomers

• Stereoisomers are compounds that have identical
  chemical components but differ in the way the
  atoms or groups are arranged in space.
• Stereoisomers fall into two broad classes
• 1) Geometric isomers and
• 2) Optical isomers

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Definition of Isomers (Contd)

• Geometric isomers are a type of stereoisomer in
  which a chemical group or atom occupies different
  spatial positions in relation to the double
  bonds. If the double bond is between two carbon
  atoms, the isomers are called cis or trans.

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Definition of Isomers (Contd)

• If the double bond is between a carbon and a
  nitrogen atom, the isomers are called anti and
  syn.
• Example

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Definition of Isomers (Contd)

• An optical isomer is compound which rotates the
  plane of polarized light.

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Definition of Isomers (Contd)

• There are two kinds of optical isomers
• 1) Diastereomers and
• 2) Enantiomers

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Definition of Isomers (Contd)

• Diastereomers are not mirror images and occur in
  compounds having two or more asymmetric carbon
  atoms or chiral center.
• Said another way, diastereomers are stereoisomers
  which are not enantiomers.
• Example Erythrose

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Definition of Isomers (Contd)

• Enantiomers are mirror image structures that
  result from the presence of one or more
  asymmetric carbon atoms in the compound.
• Example

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Pharmacokinetic Properties

• Stereoisomers may possess different
  pharmacokinetic properties, such as adsorption,
  distribution, biotransformation, and excretion.
• They may also possess, quantitatively or
  qualitatively, different pharmacologic or
  toxicologic effects.

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Technological Advances

• Technological advances now allow for the
  separation of most racemates into the
  corresponding enantiomers, and for large scale
  production of a single enantiomer.

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Technological Advances (Contd)

• As a result, it is now the accepted practice to
  separate racemates into the corresponding
  enantiomers early in drug development, and to do
  pharmacokinetic studies on the enantiomer that is
  identified as having the predominant biological
  activity.

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Claiming an Enantiomer

• Include the name or the structure of the
  enantiomeric chemical compound.
• Apply a standard convention to designate and
  name the enantiomer.
• Incorporate as much as possible of comparative,
  and especially, pharmacokinetic data into the
  specification.

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Examining the Claim

• In examining the claim to the enantiomer, the
  existence of the racemic mixture has to be
  considered.
• Because it is no longer unexpected for one
  enantiomer to posses the predominant biological
  activity, a prima facie case of obviousness may
  be made in cases where the prior art enables the
  separation of the racemic mixture into the
  corresponding enantiomer.

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Examining the Claim

• This is not a general rule and every case has to
  be weighed and considered according to the
  specific facts.
• However, an application would be more complete if
  the specification includes as much
  pharmacokinetic data as possible.
• Simply showing that one enantiomer possesses the
  predominant biological activity will normally not
  be considered sufficient to rebut a prima facie
  finding of obviousness.

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Examining the Claim

• For Example, applicants may compare the potential
  for inter-conversion, absorption, distribution,
  biotransformation, altered metabolic function,
  drug-drug interaction, and toxicity.

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QUESTIONS